With the progression of the genome sequence project, the detection of particular genes on the genome, the analysis of SNPs, and expression analysis have received attention as post-genomic challenges. Therefore, analysis methods such as a hybridization method using a microarray (DNA chip) and an in situ hybridization method have become increasingly important as methods for detecting a target sequence in recent medical and molecular biological fields. In the microarray hybridization method, probe nucleic acids binding specifically to a target substance are immobilized on a substrate, and the presence or amount of the target substance in a sample is analyzed through the hybridization of the probe nucleic acids with the sample.
In general, these hybridization reactions are carried out by dropping a target nucleic acid-containing hybridization solution onto a substrate on which probe nucleic acids binding specifically to a target nucleic acid are immobilized.
This target nucleic acid is sometimes obtained in small amounts from a sample. For example, in gene examination for identifying pathogenic bacteria of bacteremia, the number of bacteria contained in blood is approximately several to several tens of cfu/mL. Thus, these examinations using hybridization are usually performed after nucleic acid amplification for increasing the amount of a target nucleic acid. Particularly, the polymerase chain reaction (PCR method) has often been used as an amplification reaction.
Thus, analysis combining nucleic acid amplification with the hybridization reaction has problems such as complicated handling of sample solutions and contamination. In this regard, Japanese Patent Application Laid-Open No. 2004-298017 has disclosed a solid phase probe array for reaction including plural reaction portions.
However, even more than contamination and complicated procedures, a further rapid reaction has been demanded in gene examination performed particularly in clinical fields.
In this regard, a technique for accelerating each reaction at nucleic acid amplification and at hybridization has been developed so far.
For example, in regard to more rapid nucleic acid amplification, Japanese Patent Application Laid-Open No. 2005-328709 has disclosed a method for performing high-speed PCR using heat-resistant DNA polymerase having a deoxyribonucleic acid synthesis rate of 100 bases/second or more.
Examples of more rapid hybridization reaction include a method performing agitation. For example, Japanese Patent No. 3746756 has disclosed an apparatus including an operation unit for stirring a sample solution, which causes a relative motion between a table member for holding a substrate on which a probe is immobilized and a plate member provided to form space to be filled with the sample solution.
An alternative method has also been disclosed which includes efficiently performing hybridization in a short time by transferring a nucleic acid for detection by use of dielectrophoresis. For example, Japanese Patent Application Laid-Open No. 2006-047153 has disclosed a method including hybridizing a nucleic acid for detection with a target nucleic acid by applying an electric field to an opposing electrode of a DNA chip having a detection portion including the opposing electrode capable of applying an electric field to a medium held in a hybridization chamber.